Sulfonamide anti-arrhythmic agents

Abstract

A series of novel alkanesulphonamidophenyl-N-alkyl-N-(heterocyclic-alkyl) alkylamine derivatives have been prepared, including their pharmaceutically acceptable salts. These compounds are useful in therapy as anti-arrhythmic agents and therefore, are of value in the treatment of various cardiac arrythmias. Said sulfonamide base compounds are of the formula: ##STR1## wherein R and R 1 are each C 1 -C 4 alkyl; X is --CH 2 --, --CO--or --CO(OH)--; n is two, three or four; and "Het--" is a nitrogen-containing heterocyclic group wherein said heterocyclic group is phenyl or benzyl-substituted 2H-pyridazin-3-on-2-yl, or it is 2H-phthalazin-1-on-2-yl, 4-halo-2H-phthalizin-1-on-2-yl or 4-(C 1 -C 4 alkyl)-2H-phthalazin-1-on-2-yl, 2H-isoindolin-1-on-2-yl, 3H-quinazolin-4-on-3-yl, 2H-3,4-dihydroisoquinol-1-on-2-yl, 2H-isoquinol-on-2-yl, 1H-3,4-dihydroquinol-2-on-1-yl, benzoxazol-2-on-3-yl, quinol-2-on-1-yl, quinol-2-yl or indol-2-yl, each optionally mono substituted with halogen or C 1 -C 4 alkyl on the benzene portion of the respective fused ring moieties.

We claim: 
     
       1. A sulfonamide compound of the formula: ##STR63## or a pharmaceutically acceptable salt thereof, wherein R and R 1  are each C 1  -C 4  alkyl; X is --CH 2  --, --CO-- or --CH(OH)--;   n is two, three or four; and   "Het" is a nitrogen-containing heterocyclic group of the formula: ##STR64##  wherein R 2  is phenyl or benzyl; and R 3  and R 4  are each hydrogen, halogen or C 1  -C 4  alkyl.   
     
     
       2. A compound as claimed in claim 1 wherein "Het" is 5-phenyl-2H-pyridazin-3-on-2-yl, 5-benzyl-2H-pyridazin-3-on-2-yl, 4-methyl-2H-phthalazin-l-on-2-yl or 2H-phthalazin-1-on-2-yl. 
     
     
       3. A compound as claimed in claim 1 wherein R is methyl, R 1  is methyl or ethyl and n is two or three. 
     
     
       4. A compound as claimed in claim 3 wherein R 1  is methyl, n is two and X is --CH 2  -- or --CH(OH)--. 
     
     
       5. N-[2-(4-Methanesulphonamidophenyl)-2-hydroxy-ethyl]-N-methyl-2-(2H-phthalazin-1-on-2-yl)ethylamine. 
     
     
       6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and an effective anti-arrhythmic amount of a compound as claimed in claim 1. 
     
     
       7. A method for preventing or reducing cardiac arrhythmias in the treatment of a subject afflicted with an impaired cardiac pump function, which comprises administering to said subject an effective anti-arrhythmic amount of a compound as claimed in claim 1. 
     
     
       8. A compound as claimed in claim 1 wherein "Het" is 5-phenyl-2H-pyridazin-3-on-2-yl, 5-benzyl-2H-pyridazin-3-on-2-yl, 4-methyl-2H-phthalazin-1-on-2-yl or 2H-phthalazin-1-on-2-yl, R and R 1  are each methyl, n is two and x is --CH(OH)--.